**4. Clinical implications of anti-NPA antibodies and future research directions**

IgG anti-NPA antibodies were detected in the sera from patients that were positive for IgM or IgG anti-cardiolipin antibodies [53]. Some of these patients met four or more of the SLE criteria established by the American Rheumatism Association [54], others met the criteria for primary antiphospholipid syndrome [39], and others met the criteria for secondary antiphospholipid syndrome associated to SLE [39]. The presence of anti-NPA antibodies suggests that the NPA on the cell membranes of these patients had been stabilized; however, what led to this stabilization has not yet been identified. For example, in leprosy patients where anti-NPA antibodies have been detected, one factor that could induce the formation and stabilization of the NPA is the mycolic acid from the mycobacteria [55]. Since anti-NPA antibodies trigger a lupus-like disease in mice, it would be important to measure these antibodies in a larger number of SLE patients and in patients with other types of lupus, in order to identify if there is a relationship between the levels of these antibodies and the severity of the disease. If the anti-NPA antibodies are detected earlier than other autoantibodies (anti-cardiolipin, anti-histones, anti-coagulant) in patients with SLE, as it occurs in the mouse model, they could be used for the early detection of the disease, so that the patients could receive the appropriate treatment to prevent disease complications [53]. It also remains to be determined if the levels of IgG anti-NPA antibodies are increased in patients with drug-induced lupus, compared to patients with non-drug related SLE, if high levels of anti-NPA antibodies correlate with a specific clinical phenotype of lupus, and if the levels of these antibodies could be used as biomarkers to monitor treatment response in these patients.
